6-(1-Carbamoyl-1-hydroxymethyl)penicillanic acid derivatives, having the partial structure ##STR1## wherein n is 0, 1 or 2, are generally useful as antibacterials and/or beta-lactamase inhibitors. Some of these compounds possess excellent antibacterial activity per se, and so are valuable as industrial or medicinal antibacterial agents in their own right. Additionally, and more generally, they have particular value as beta-lactamase inhibitors; as such, they are useful in combination with conventional beta-lactam antibiotics (penicillins and cephalosporins) against microorganisms resistant or partially resistant to beta-lactam antibiotics through production of beta-lactamase enzymes.
beta-Lactamase inhibiting 6-(1-hydroxyalkyl)penicillanic acid 1,1-dioxides (sulfones) and 3-carboxylate esters thereof have been reported by Kellogg (U.S. Pat. Nos. 4,287,181; 4,342,768; European Pat. Publication No. 83977), while 6-(aminoacyloxymethyl)penicillanic acid 1,1-doxides have been reported by Barth (U.S. Pat. No. 4,503,040). Various antibacterial 6-(1-hydroxyalkyl)penicillanic acids and their 1-oxides (sulfoxides) have been disclosed by Beattie et al., (U.S. Pat. No. 4,207,323), but that disclosure encompasses no compounds containing the key 6-(1-carbamoyl-1-hydroxyalkyl)substituent of the present invention.
U.K. Patent Application No. 2,053,220 broadly discloses beta-lactamase inhibiting compounds of the formula ##STR2## The definitions of R.sub.a, R.sub.b and R.sub.c define literally an infinite number of compounds. Said infinity of compounds proposed might be construed to encompass some of the 1,1-dioxide compounds of the present invention. However, there is no specific mention of or preparative method provided for any compounds of the type of the present invention, let alone any hint or suggestion that the present compounds represent preferred compounds, having potent antibacterial and/or beta-lactamase inhibitory activity.
Sheehan et al. [J. Antibiotics Japan, vol. 37, pp. 1441-1448 (1984)] have reported that 6-[1-(N-phenylcarbamoyl)methyl]penicillanic, a compound lacking the present 1-hydroxy group, possesses only limited Gram-positive activity and no Gram-negative activity. Sheehan et al. do not list the latter compound among those having a modicum of beta-lactamase inhibitory activity.